Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland.
J Hypertens. 2022 Jan 1;40(1):46-64. doi: 10.1097/HJH.0000000000002972.
In this study, we hypothesized that excitatory reno-renal reflex control of sympathetic outflow is enhanced in rats exposed to chronic intermittent hypoxia (CIH) with established hypertension.
Under anaesthesia, renal sensory nerve endings in the renal pelvic wall were chemically activated using bradykinin (150, 400 and 700 μmol/l) and capsaicin (1.3 μmol/l), and cardiovascular parameters and renal sympathetic nerve activity (RSNA) were measured.
CIH-exposed rats were hypertensive with elevated basal heart rate and increased basal urine flow compared with sham. The intrarenal pelvic infusion of bradykinin was associated with contralateral increase in the RSNA and heart rate, without concomitant changes in blood pressure. This was associated with a drop in the glomerular filtration rate, which was significant during a 5 min period after termination of the infusion but without significant changes in urine flow and absolute sodium excretion. In response to intrarenal pelvic infusion of 700 μmol/l bradykinin, the increases in RSNA and heart rate were blunted in CIH-exposed rats compared with sham rats. Conversely, the intrarenal pelvic infusion of capsaicin evoked an equivalent sympathoexcitatory effect in CIH-exposed and sham rats. The blockade of bradykinin type 1 receptors (BK1R) suppressed the bradykinin-induced increase in RSNA by ∼33%, with a greater suppression obtained when bradykinin type 2 receptors (BK2R) and BK1R were contemporaneously blocked (∼66%).
Our findings reveal that the bradykinin-dependent excitatory reno-renal reflex does not contribute to CIH-induced sympathetic hyperactivity and hypertension. Rather, there is evidence that the excitatory reno-renal reflex is suppressed in CIH-exposed rats, which might relate to a downregulation of BK2R.
在这项研究中，我们假设在慢性间歇性低氧（CIH）合并高血压的大鼠中，肾-肾反射兴奋对交感神经输出的控制增强。
在麻醉下，使用缓激肽（150、400 和 700 μmol/L）和辣椒素（1.3 μmol/L）化学激活肾盂壁中的肾感觉神经末梢，并测量心血管参数和肾交感神经活动（RSNA）。
与假手术组相比，CIH 暴露组大鼠血压升高，基础心率升高，基础尿量增加。肾内骨盆输注缓激肽与对侧 RSNA 和心率增加相关，血压无变化。这与肾小球滤过率下降有关，在输注结束后 5 分钟内显著，但尿量和绝对钠排泄无明显变化。与假手术组相比，CIH 暴露组大鼠肾内骨盆输注 700 μmol/L 缓激肽后，RSNA 和心率的增加减弱。相反，肾内骨盆输注辣椒素在 CIH 暴露和假手术大鼠中引起等效的交感兴奋作用。缓激肽 1 型受体（BK1R）阻断抑制了缓激肽诱导的 RSNA 增加约 33%，当同时阻断缓激肽 2 型受体（BK2R）和 BK1R 时，抑制作用更大（约 66%）。
我们的发现表明，缓激肽依赖性兴奋肾-肾反射不会导致 CIH 引起的交感神经活性增加和高血压。相反，有证据表明，CIH 暴露大鼠的兴奋肾-肾反射受到抑制，这可能与 BK2R 的下调有关。
